The conversion of azathioprine (AZA) to active 6-thioguanine nucleotides (6-TGN) is essential for its clinical efficacy; however, another metabolite formed, 6-methylmercaptopurine (6-MMP), is related to hepatotoxicity. Blood samples were collected from 37 patients under AZA’s treatment, and a new HPLC-UV method was validated and applied for simultaneous quantification of 6-TGN and 6-MMP in erythrocytes of Crohn’s disease (CD) patients. The concentration of 6-TGN and 6-MMP found ranged from 4.5 to 2,456 ρmol/8 × 108 red blood cells (RBCs) for 6-TGN and from 170 to 53,951 ρmol/8 × 108 RBCs for 6-MMP. Reduced levels of 6-MMP in patients into combo therapy with AZA and allopurinol (2,031 ρmol/8 × 108 RBCs) have been observed when compared to patients undergoing monotherapy with AZA (9,098 ρmol/8 × 108 RBCs). Additionally, there was a negative correlation (r = −83.7%, P < 0.05) between lymphocyte count and 6-TGN levels. The method developed is reliable, accurate and reproducible and can be used as an important tool in the monitoring routine of patients with CD under AZA treatment, allowing the individualization of the dose, monitoring adherence to the treatment and the evaluation of the clinical outcome of these patients.

中文翻译：

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HPLC-UV同时监测克罗恩病患者红细胞中硫唑嘌呤代谢物

硫唑嘌呤 (AZA) 转化为活性 6-硫鸟嘌呤核苷酸 (6-TGN) 对其临床疗效至关重要；然而，形成的另一种代谢物 6-甲基巯基嘌呤 (6-MMP) 与肝毒性有关。对接受 AZA 治疗的 37 名患者采集血样，验证并应用一种新的 HPLC-UV 方法同时定量克罗恩病 (CD) 患者红细胞中的 6-TGN 和 6-MMP。6-TGN 和 6-MMP 的浓度范围为 4.5 至 2,456 ρmol/8 × 108 红细胞 (RBC)，6-TGN 为 170 至 53,951 ρmol/8 × 108 RBC，6-MMP。与接受 AZA 单药治疗的患者（9,098 ρmol/8 × 108 RBCs）相比，在接受 AZA 和别嘌呤醇联合治疗（2,031 ρmol/8 × 108 RBCs）的患者中观察到 6-MMP 水平降低。此外，淋巴细胞计数与 6-TGN 水平呈负相关（r = -83.7%，P < 0.05）。所开发的方法可靠、准确且可重复，可用作对接受 AZA 治疗的 CD 患者进行常规监测的重要工具，允许个体化剂量、监测治疗依从性和评估这些患者的临床结果患者。